Pure red cell aplasia (PRCA), is a very rare disorder of the bone marrow, in which your bone marrow is not able to produce enough red blood cells. This can be quite concerning because your red blood cells (RBCs) are responsible for carrying oxygen to all the organs of your body and without RBCs, your oxygen supply can be hindered. 

At times, PRCA can be inherited or it can be acquired later in life, often in conjunction with another disorder. A large number of cases of PRCA may also be idiopathic, which means that no known cause has been discerned.

Understanding pure red cell aplasia

Our blood is made up of a mix of different things and one of the main components of blood is RBCs. These carry oxygen which we breathe in from the lungs and deliver to all parts of the body. Oxygen is essential to our organs and cells, in order to carry out all their vital functions. RBCs, as well as all other blood cells (such as white blood cells and platelets), are produced by the core part of our bones which is known as the bone marrow. In PRCA, the bone marrow does not produce sufficient RBCs because there is a disruption in erythropoiesis (which is the process by which RBCs are made) but the levels of white blood cells and platelets in the blood are normal. There will also be a decrease in the immature RBCs which are known as reticulocytes. 

PRCA occurs predominantly in adults and as stated above, it can be inherited or acquired later in life. The acquired form of this disorder is known as Diamond-Blackfan or Blackfan-Diamond syndrome.

If you acquire this later in life, it can happen in conjunction with multiple different reasons such as:¹

• Various blood cancers such as leukaemia 
• Solid cancers/tumours such as breast, renal, thyroid etc 
• Autoimmune disorders such as rheumatoid arthritis, inflammatory bowel disease etc 
• Lymphoproliferative disorders 
• Viral infections, usually from parvovirus B19. This viral infection leading to PRCA usually occurs in people who have weakened immune systems or a previous medical condition affecting the bone marrow. 
• Bacterial infections from bacteria such as tuberculosis 
• Certain medications such as recombinant erythropoietin (rhEPO), immunosuppressive drugs, anticonvulsants 
• Pregnancy 
• Riboflavin deficiency 

PRCA usually presents in a person, as normal anaemia would. Some signs and symptoms which can occur are: 

• Tiredness and fatigue
• Dizziness
• Pale skin
• Headaches 
• Dyspnea (difficulty breathing)

Diagnostic approaches 

The symptoms listed above are not conclusive of PRCA, which means if you experience these symptoms, it does not necessarily mean that you have this disorder. A proper physical examination and blood tests would be needed for a more accurate diagnosis.² Your doctor might suggest the following tests: 

• Complete Blood Count - this might show a decreased number of red blood cells 
• Reticulocyte count - this would show a decreased amount of reticulocytes which is known as reticulocytopenia.
• Peripheral Blood smear
• Bone marrow aspiration biopsy 
• Tests for various bacteria and viruses which can cause PRCA such as parvovirus 
• CT scan

A bone marrow aspiration and biopsy can confirm the diagnosis of PRCA. There are a lot of medical conditions which can cause a decrease in red blood cell count, but in PRCA a biopsy will show a decreased reticulocyte count in an otherwise completely normal bone marrow. 

Treatment strategies 

The treatment strategy for treating PRCA largely depends on how you contracted it, whether it was acquired at birth or whether it developed later in life due to a disease or virus. Some treatment strategies which your doctor might suggest are: 

• Immunosuppressants: these are medications which can suppress your immune system and they may be useful in treating PRCA which has been contracted secondary to an autoimmune disorder. Some examples may include cyclosporine or corticosteroids and you might require several sessions of this treatment before you notice any improvements 
• Stem cell transplant: if you inherited this disorder, you will most probably need a stem cell transplant. In this process, the damaged blood cells in the bone marrow are replaced by healthy ones.³ This treatment can also be useful in treating PRCA which is caused secondary to blood cancers. 
• Immunoglobulin therapy: this type of treatment is mostly used if you have contracted PRCA due to parvovirus B19. Immunoglobulins can help to stop the virus from destroying red blood cells. 
• Surgery: at times surgery might be useful, especially in removing solid cancers 
• Blood transfusions: this method is the mainstay of increasing the number of red blood cells in the blood. If you do not respond to any other treatment, you may need regular blood transfusions to minimise your symptoms. 

Complications 

Although regular blood transfusions can greatly help people who suffer from PRCA and provide relief from the symptoms associated with it, there are also some complications and side effects which can occur. 

Some common side effects are fever, chills, rash and itchiness. These are mild and often go away on their own with little or no treatment. However, at times more serious complications can occur. 

One of these can include acute (ATR) or delayed (DTR) transfusion reactions;⁴ ATR occurs within 24 hours of transfusion and DTR occurs 24 hours to 30 days after the transfusion. ATR symptoms can include a burning sensation, chills, headaches, nausea/vomiting, hypotension, tachycardia and a reddish colour to the urine. DTR can exhibit symptoms similar to those shown by ATR but they are often mild. These transfusion reactions can range from mild to severe and can even be life-threatening so they must be treated urgently, with the immediate discontinuation of the transfusion. 

There is also the risk of contracting diseases which can be transmitted through blood transfusions. Some examples include HIV and hepatitis B virus and the patient would start to exhibit symptoms of the disease they have contracted. The NHS screens donor blood in order to minimise this risk; you can read more about this here. 

Another common risk of blood transfusions is iron overload.⁵ There is a lot of iron in blood and getting regular transfusions of blood may cause your body to accumulate excess iron. This extra iron can gather in your organs and cause them damage. This iron overload in the body can be treated with iron chelation drugs. These drugs remove the excess iron from the blood by encouraging its excretion from the body through urine and bile. These iron chelators are given either by tablets or a small portable pump which can administer the drug subcutaneously (under the skin). Hence, people who are receiving iron chelators need to be compliant with their medication, otherwise the iron overdose will not be reduced. 

Your doctor will decide whether or not you require iron-chelating drugs after a blood transfusion by conducting a series of blood tests. In the beginning, the symptoms of iron overload are quite general such as: 

• Fatigue
• Weight loss
• Abdominal or joint pain 
• Loss of sex drive 

But as the condition progresses more, the symptoms get more severe and can include: 

• A grey or bronze tinge to the skin
• Shortness of breath
• Liver disease 
• Enlarged spleen
• Arthritis 
• Heart disease 

If iron overload occurs in a young person, they might experience delayed puberty or women might experience a disruption in their menstrual cycle. 

Prognosis 

The prognosis and outlook of PRCA largely depend on the underlying cause, and whether this disease was inherited or acquired.¹ For example, people who inherit this disorder and respond well to treatment, without the need for regular blood transfusions can live a normal life span. People who receive successful stem cell transplants also have a good life expectancy. On the other hand, if they do not respond ideally to treatment or require blood transfusions alongside their treatments, their life span can decrease to roughly 30 to 40 years. 

People who acquire this disease due to an underlying infection from viruses or bacteria, riboflavin deficiency, or pregnancy have a better prognosis and normal life expectancy, after treatment of the underlying conditions. However, if PRCA develops due to cancers or autoimmune disorders, the prognosis and life expectancy can be shorter. 

Conclusion 

PRCA is a rare disorder that causes a reduced amount of red blood cells in the blood. The bone marrow is normal and produces a normal amount of other blood cells such as white blood cells and platelets, but there is a decreased amount of reticulocytes which is seen. PRCA can be either inherited from your parents or acquired later in life due to some diseases. 

RBCs are responsible for carrying oxygen to all parts of the body so PRCA can cause signs and symptoms of anaemia. These symptoms are quite general and the blood tests conducted can also be quite general, so a bone marrow aspiration and biopsy will be required. This will show a normal bone marrow with decreased reticulocyte count. 

There are several different treatments available to treat PRCA but some patients might not respond well to treatment or have severe PRCA and require regular blood transfusions alongside their treatment. Blood transfusions can reduce the symptoms but they also cause a number of complications, which will need to be treated as well. 

The outlook for PRCA is not completely dire, and if proper treatment is established and the patient responds well to it and does not require additional blood transfusions, the prognosis can be quite good. In fact, people affected by this can even live a normal life span if they respond well to treatment.